City of Hope presents new cancer research at American Society of Clinical Oncology meeting

Findings on blood, breast, lung and bladder cancers will be presented at ASCO’s annual conference

DUARTE, Calif. — City of Hope doctors and researchers will present their latest research on immunotherapy, precision medicine and other topics during the American Society of Clinical Oncology’s Annual Meeting June 3 to 7 in Chicago. An estimated 30,000 oncology professionals attend the conference to learn about the latest scientific research on cancer treatment, detection and prevention.

Significant City of Hope presentations at this year’s meeting include:

Preliminary results of a phase I/II study supporting use of ixazomib, pomalidomide and dexamethasone for relapsed/refractory multiple myeloma

Biomarker is linked to survival and treatment response for BRCA-positive breast cancer patients

New and emerging targets for advanced bladder cancers: BGJ398

Veliparib used in combination with chemotherapy and radiation for patients with unresectable Stage 3 nonsmall cell lung cancer

“The cancer death rate has declined in the last 50 years — due in large part to early cancer detection, more prevention efforts and better treatments — but more work remains to be done,” said Steven T. Rosen, M.D., City of Hope’s provost and chief scientific officer. “The ASCO annual meeting brings together leading cancer researchers and clinicians, inspiring collaboration and renewing our commitment to finding the most effective cancer treatments so we can achieve a meaningful, tangible impact against the disease.”

City of Hope researchers have found encouraging responses to a novel oral combination treatment for patients with multiple myeloma that has returned or no longer responds to other standard treatments.

Amrita Krishnan, M.D., director of the Judy and Bernard Briskin Center for Multiple Myeloma Research, and colleagues at three other multiple myeloma research foundation centers (Sarah Cannon, Mayo Clinic, Emory Healthcare) studied 32 patients with relapsed or refractory multiple myeloma who took an oral regimen as part of a phase I/II clinical trial. The treatment combines ixazomib, the first oral proteasome inhibitor approved by the Food and Drug Administration (FDA) in late 2015; pomalidomide, an immunomodulatory agent, and dexamethasone, a steroid that can augment the effects of ixazomib and pomalidomide.

Patients were able to take the three drug combination with only mild side effects, and did not experience significant nausea or increased nerve damage. More than 70 percent of the patients had a clinical benefit after taking the drugs. While the results reported are still preliminary — many patients just finished one cycle of therapy — Krishnan said investigators are encouraged by the response rate.

“There’s a lot of hope for new treatments for patients whose multiple myeloma has returned or who no longer respond to other treatments because of the recent approval of several new drugs for relapsed myeloma,” said Krishan, also a professor in City of Hope’s Department of Hematology and Hematopoietic Cell Transplantation. “Our regimen is particularly attractive as it is entirely oral, thereby allowing patients much more freedom to maintain their lifestyle.”

Based on these findings, Krishnan said the team will continue to study patient response rates for a longer period of time and why some patients respond better to the treatment than others.

Robert Chen, M.D., assistant professor with City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation, and colleagues conducted a multicenter phase II trial that examined the efficacy and safety of pembrolizumab in 180 patients with relapsed/refractory Hodgkin lymphoma. Pembrolizumab is an immunomodulatory drug that bolsters the body’s immune system to fight cancer cells. The trial is a pivotal study that could lead to the FDA’s approval of the drug for use by patients with Hodgkin lymphoma.

The study included three groups of patients: 1) patients whose disease relapsed after stem cell transplant and didn’t respond to brentuximab vedotin, an antibody-drug conjugate, 2) patients who were ineligible for a stem cell transplant and didn’t respond to brentuximab vedotin; and 3) patients whose disease relapsed after stem cell transplant and have not taken brentuximab vedotin.

Patients tolerated the drug well, and side effects were minimal. In addition, the tumors of between 70 to 80 percent of the patients in each group shrank by at least 50 percent. Up to 30 percent of patients in each group went into remission after taking pembrolizumab.

The drug works by targeting a protein known as PD1 on the surface of T cells.

“Normally, when the body’s immune system sees a cancer cell, it’s supposed to say this is a bad cell and kill it,” Chen said. “But PDL1, which is expressed on the tumor cells, binds to PD1 on the T cells, fools the immune system into thinking the tumor cell is a good one and doesn’t kill it.”

Pembrolizumab prevents PD1 from attaching itself to PDL1, thus enabling the immune system to continue to attack tumor cells.

A phase III, randomized trial of the drug is being planned that will compare pembrolizumab and brentuximab vedotin in treating Hodgkin lymphoma patients.

“Immunotherapy agents have opened a lot of doors for patients, and they are generally well-tolerated,” Chen said. “They hold a lot of promise.”

A study led by Jeffrey Weitzel, M.D., director of City of Hope’s Division of Clinical Cancer Genetics, found that for breast cancer patients with BRCA gene mutations, compounds called poly ADP ribose (PAR) can help determine treatment response and clinical outcomes.

PAR is produced by enzymes called PARP, which are also involved in DNA repair and programmed cell death. Cancer cells can also exploit PARP to repair themselves after DNA damage from radiation or chemotherapy. To address this, a new class of drugs called PARP inhibitors have been developed to thwart this self-repair process, which can enhance current cancer therapies or kill the cancer cells outright.

For the study, 72 patients with BRCA-associated metastatic breast cancer were treated with either veliparib, a PARP inhibitor, on its own or with carboplatin, a chemotherapy drug. The patients also had their PAR levels measured before treatment, three hours after treatment and at additional times later on.

After capturing and analyzing these measurements, Weitzel and his team found that patients who survived longer or had better treatment responses either have higher PAR levels before treatment or a greater drop in PAR levels after the initial veliparib therapy.

Weitzel said the findings can be used to determine which breast cancer patients are most likely to benefit from PARP inhibitor therapy, and is currently studying whether this therapy will be beneficial as a first-line treatment or in BRCA-associated breast cancer in earlier stages.

By molecularly profiling his patients with advanced bladder cancer, Pal has found that many of them — about 20 percent — have alterations in a gene called FGRF3. Patients with this specific alteration were treated with a drug called BGJ398 in a City of Hope-led clinical trial have shown impressive efficacy with this particular therapeutic agent.

“In one case, we actually observed a complete response to the therapy, which is rarely encountered in the setting of advanced bladder cancer,” Pal said.

The results from the clinical trial represents a significant change in the treatment of bladder cancer, which for over three decades has had very little progress in treatment advances.

A phase I study funded by the National Cancer Institute and conducted by Southwest Oncology Group (SWOG) in patients with unresectable stage 3 nonsmall cell lung cancer evaluated the use of the PARP enzyme inhibitor veliparib in combination with standard chemotherapy and radiation. Limited treatment options are available for patients with this type of cancer.

This multicenter study found patients can tolerate oral veliparib during chemotherapy and radiation, and also established a safe dose amount, said Mihaela Cristea, M.D., an associate clinical professor in City of Hope’s Department of Medical Oncology & Therapeutics Research and the study’s principal co-investigator. A phase II study is being planned and will test the drug’s effectiveness.

Veliparib works by inhibiting the PARP enzyme, thereby preventing the repair of DNA in cancer cells. Preclinical studies demonstrated that veliparib can augment the effects of radiation and certain chemotherapy drugs, including carboplatin, which was used in the study.

About City of Hope
City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 45 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout Southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation,diabetes and numerous breakthrough cancer drugs based on technology developed at the institution. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.
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